Action Points

Explain to interested patients that screening has been shown to reduce mortality in several forms of cancer, but not in lung cancer.

Note that this study shows a sharp increase in the detection of small cancers and surgery to remove them, but did not demonstrate a reduction in overall mortality.

NEW YORK, March 6 -- CT-scan screening dramatically increases the number of small lung cancers detected and the rate of curative surgery, according to researchers here.

But in a combined analysis of three single-institution studies, screening had no effect on the lung cancer mortality rate or on the rate of late-stage lung cancer diagnosis, found Peter Bach, M.D., of Memorial Sloan-Kettering Cancer Center.

The finding implies that the additional small cancers detected by CT screening are unlikely to grow rapidly enough to significantly affect lung cancer mortality overall, Dr. Bach and colleagues reported in the March 7 issue of the Journal of the American Medical Association.

"Early detection and additional treatment did not save lives but did subject patients to invasive and possibly unnecessary treatments," Dr. Bach said.

"Ours is the first study to ask whether detecting very small growths in the lung by CT is the same as intercepting cancers before they spread and become incurable," Dr. Bach said. "We found an answer and it was, 'no'."

But Dr. Bach and colleagues said the contradiction may be only apparent, because prolonged survival of lung-cancer patients is necessary but not sufficient for there to be an effect on overall mortality.

To lower mortality, the authors argued, "computed tomography screening must also intercept at an early stage those cancers that will later progress to cause clinical disease and death, and in our study, CT screening did not intercept these cancers."

In fact, they said, few of the patients who eventually died of lung cancer in the three cohorts were among those diagnosed by CT screening and subsequently treated for early lung cancer.

The three cohorts -- at the Instituto Tumori in Milan, Italy, the Mayo Clinic in Rochester, Minn., and the Moffitt Cancer Center in Tampa, Fla. -- included a total of 3,246 asymptomatic men and women (median age of 60) who had smoked or still smoked for an average of 39 years.

The volunteers were given annual CT scans and Dr. Bach and colleagues compared their lung cancer outcomes (from national vital statistics databases) with a validated model of lung cancer.

The analysis found that after a median follow-up of 3.9 years:

144 volunteers were diagnosed with lung cancer, compared with 44.5 expected cases. The relative risk was 3.2, with a 95% confidence interval from 2.7 to 3.8, which was significant at P<0.001.

109 individuals had a lung resection, compared with the expected 10.9. The relative risk was 10.0, with a 95% confidence interval from 8.2 to 11.9, which was significant at P<0.001.

42 people -- compared with an expected 33.4 -- were diagnosed with advanced lung cancer and 38 died of lung cancer, compared with an expected 38.8. Neither difference was statistically significant.

"Our findings are consistent with the results of earlier studies of lung cancer screening with chest x-rays, which showed no benefit to this type of screening for current and former smokers," said senior author Colin Begg, Ph.D., also of Memorial Sloan-Kettering.

Although there are several possible reasons for the disparity between the current study and the earlier I-ELCAP study, the most likely is the different endpoints -- overall mortality versus individual survival -- according to William Black, M.D., of the Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and John Baron, M.D., of Dartmouth Medical School in Hanover, N.H.

"Prolonged survival need not imply reduced mortality," they said in an accompanying editorial, noting that in the Bach study four-year survival was a "remarkably high" 94% among clinical stage I lung cancer patients who had surgery, even though there was no reduction in lung cancer mortality.

On the other hand, they said, the study also "provides insight into the potential harms of CT screening," including the mortality and morbidity associated with a 10-fold increase in lung resections.

The researchers reported no financial conflicts. The study was supported by the four involved institutions, the Steps for Breath fund at Memorial Sloan-Kettering Cancer Center, European Institute of Oncology, the Italian Ministry of Health, the National Cancer Institute, the Department of Defense, and the National Cancer Institute. Dr. Baron reported no financial disclosures but Dr. Black said he was briefly involved as a potential expert witness for Phillip Morris in a lawsuit concerning lung cancer screening. He withdrew and returned his fee in order to avoid the appearance of being supportive of the tobacco industry.

Reviewed by Zalman S. Agus, MD Emeritus Professor at the University of Pennsylvania School of Medicine

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